RU2220980C2 - Chimeric antibody that binds with human cd40 (variants), nucleic acid molecule (variants), expression vector (variants), humanized antibody (variants), pharmaceutical composition for treatment of disease mediated by t-cells (variants), method for treatment of patient with diseases mediated by t-cells (variants) - Google Patents

Chimeric antibody that binds with human cd40 (variants), nucleic acid molecule (variants), expression vector (variants), humanized antibody (variants), pharmaceutical composition for treatment of disease mediated by t-cells (variants), method for treatment of patient with diseases mediated by t-cells (variants) Download PDF

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RU2220980C2
RU2220980C2 RU2000124084/13A RU2000124084A RU2220980C2 RU 2220980 C2 RU2220980 C2 RU 2220980C2 RU 2000124084/13 A RU2000124084/13 A RU 2000124084/13A RU 2000124084 A RU2000124084 A RU 2000124084A RU 2220980 C2 RU2220980 C2 RU 2220980C2
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Алехандро А. АРАФФО (US)
Алехандро А. АРАФФО
Диан ХОЛЛЕНБОГ (US)
Диан ХОЛЛЕНБОГ
Энтони В. СИАДЭК (US)
Энтони В. СИАДЭК
Карен К. БЕРРИ (US)
Карен К. БЕРРИ
Линда Дж. ХАРРИС (US)
Линда Дж. ХАРРИС
Барбара А. ТОРН (US)
Барбара А. ТОРН
Юрген БАЖОРАТ (US)
Юрген БАЖОРАТ
Уиль м Д. ХЬЮЗ (US)
Уильям Д. ХЬЮЗ
Херрен ВУ (US)
Херрен ВУ
Джефри Д. УОТКИНС (US)
Джефри Д. УОТКИНС
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Бристол-Маерс Сквибб Компани
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    • C07—ORGANIC CHEMISTRY
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    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

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Abstract

FIELD: molecular biology, medicine, pharmacy. SUBSTANCE: invention relates to new chimeric and humanized antibodies showing specificity to human CD40 that block interaction between gp39 and CD40. Proposed antibodies raised for CD40 are effective in modulating humoral immune response to antigens depending on T-cells in case of collagen-induced arthritis, in prevention for rejection of skin transplants. Indicated antibodies can be useful owing to their anti-inflammatory properties in pharmaceutical composition and method for treatment of disease mediated by T-cells. EFFECT: valuable biological and medicinal properties of antibody, enhanced effectiveness of treatment. 27 cl, 4 tbl, 33 dwg, 5 ex

Description

Текст описания в факсимильном виде (см. графическую часть)р Description text in facsimile form (see graphic part) p

Claims (27)

1. Химерное антитело, которое связывается с CD40 человека, содержащее вариабельный участок легкой цепи с аминокислотной последовательностью SEQ ID NO:1 (фиг.4а), или его биологически активный фрагмент.1. Chimeric antibody that binds to human CD40 containing a variable region of the light chain with the amino acid sequence of SEQ ID NO: 1 (figa), or its biologically active fragment. 2. Химерное антитело, которое связывается с СD40 человека, содержащее вариабельный участок тяжелой цепи с аминокислотной последовательностью SEQ ID NO:2 (фиг.4b), или его биологически активный фрагмент.2. A chimeric antibody that binds to human CD40 containing a heavy chain variable region with the amino acid sequence of SEQ ID NO: 2 (FIG. 4b), or a biologically active fragment thereof. 3. Химерное антитело, которое связывается с CD40 человека, содержащее легкую и тяжелую цепи, причем указанная легкая цепь содержит вариабельный участок с аминокислотной последовательностью SEQ ID NO:1.3. Chimeric antibody that binds to human CD40 containing light and heavy chains, said light chain containing a variable region with the amino acid sequence of SEQ ID NO: 1. 4. Химерное антитело, которое связывается с CD40 человека, содержащее легкую и тяжелую цепи, причем тяжелая цепь содержит вариабельный участок с аминокислотной последовательностью SEQ ID NO:2.4. Chimeric antibody that binds to human CD40 containing light and heavy chains, the heavy chain containing a variable region with the amino acid sequence of SEQ ID NO: 2. 5. Химерное антитело, которое связывается с CD40 человека, содержащее легкую и тяжелую цепи, причем легкая цепь содержит вариабельный участок с аминокислотной последовательностью SEQ ID NO:1, а тяжелая цепь содержит вариабельный участок с аминокислотной последовательностью SEQ ID NO:2.5. A chimeric antibody that binds to human CD40 containing light and heavy chains, wherein the light chain contains a variable region with the amino acid sequence of SEQ ID NO: 1, and the heavy chain contains a variable region with the amino acid sequence of SEQ ID NO: 2. 6. Химерное антитело, которое связывается с CD40 человека, содержащее легкую и тяжелую цепи, причем указанная легкая цепь содержит полную аминокислотную последовательность SEQ ID NO:4 или ее биологически активный фрагмент, а указанная тяжелая цепь содержит полную аминокислотную последовательность SEQ ID NO:3 или ее биологически активный фрагмент.6. A chimeric antibody that binds to human CD40 containing light and heavy chains, said light chain containing the complete amino acid sequence of SEQ ID NO: 4 or a biologically active fragment thereof, and said heavy chain containing the complete amino acid sequence of SEQ ID NO: 3 or its biologically active fragment. 7. Химерное антитело по п.6, содержащее легкую цепь с аминокислотной последовательностью SEQ ID NO:4 и тяжелую цепь с аминокислотной последовательностью SEQ ID NO:3.7. The chimeric antibody according to claim 6, containing a light chain with the amino acid sequence of SEQ ID NO: 4 and a heavy chain with the amino acid sequence of SEQ ID NO: 3. 8. Молекула нуклеиновой кислоты, представляющая собой нуклеотидную последовательность, кодирующую вариабельный участок легкой цепи с последовательностью SEQ ID NO:1, и имеющая последовательность нуклеотидов SEQ ID NO:6.8. A nucleic acid molecule that is a nucleotide sequence encoding a variable region of the light chain with the sequence of SEQ ID NO: 1, and having the nucleotide sequence of SEQ ID NO: 6. 9. Молекула нуклеиновой кислоты, представляющая собой нуклеотидную последовательность, кодирующую вариабельный участок тяжелой цепи с последовательностью SEQ ID NO:2, и имеющая последовательность нуклеотидов SEQ ID NO:5.9. A nucleic acid molecule that is a nucleotide sequence encoding a variable region of the heavy chain with the sequence of SEQ ID NO: 2, and having the nucleotide sequence of SEQ ID NO: 5. 10. Вектор экспрессии, содержащий последовательность нуклеиновой кислоты по п.8.10. An expression vector containing the nucleic acid sequence of claim 8. 11. Вектор экспрессии, содержащий последовательность нуклеиновой кислоты по п.9.11. The expression vector containing the nucleic acid sequence according to claim 9. 12. Гуманизированное антитело, которое связывается с СD40 человека, содержащее фрагмент вариабельного участка легкой цепи с последовательностью SEQ ID NO:1.12. Humanitariannet antibody that binds to human CD40 containing a fragment of the variable region of the light chain with the sequence of SEQ ID NO: 1. 13. Гуманизированное антитело, которое связывается с CD40 человека, содержащее вариабельный участок легкой цепи с последовательностью SEQ ID NO:8.13. Humanitariannet antibody that binds to human CD40 containing the variable region of the light chain with the sequence of SEQ ID NO: 8. 14. Гуманизированное антитело, которое связывается с CD40 человека, содержащее вариабельный участок тяжелой цепи с последовательностью SEQ ID NO:10.14. Humanitariannet antibody that binds to human CD40 containing a variable region of the heavy chain with the sequence of SEQ ID NO: 10. 15. Гуманизированное антитело, которое связывается с CD40 человека, содержащее вариабельный участок легкой цепи с последовательностью SEQ ID NO:8 и вариабельный участок тяжелой цепи с последовательностью SEQ ID NO:10.15. Humanitariannet antibody that binds to human CD40 containing the variable region of the light chain with the sequence of SEQ ID NO: 8 and the variable region of the heavy chain with the sequence of SEQ ID NO: 10. 16. Гуманизированное антитело, которое связывается с CD40 человека, содержащее вариабельный участок легкой цепи с последовательностью SEQ ID NO:12.16. A humanized antibody that binds to human CD40 containing a variable region of the light chain with the sequence of SEQ ID NO: 12. 17. Гуманизированное антитело, которое связывается с CD40 человека, содержащее вариабельный участок легкой цепи с последовательностью SEQ ID NO:12 и вариабельный участок тяжелой цепи с последовательностью SEQ ID NO:10.17. Humanitariannet antibody that binds to human CD40 containing the variable region of the light chain with the sequence of SEQ ID NO: 12 and the variable region of the heavy chain with the sequence of SEQ ID NO: 10. 18. Гуманизированное антитело, которое связывается с CD40 человека, содержащее фрагмент вариабельного участка тяжелой цепи с последовательностью SEQ ID NO:2.18. Humanitariannet antibody that binds to human CD40 containing a fragment of the variable region of the heavy chain with the sequence of SEQ ID NO: 2. 19. Гуманизированное антитело, которое связывается с CD40 человека, содержащее вариабельный участок легкой цепи с последовательностью SEQ ID NO:8 и фрагмент вариабельного участка тяжелой цепи с последовательностью SEQ ID NO:1.19. A humanized antibody that binds to human CD40 containing a variable region of the light chain with the sequence of SEQ ID NO: 8 and a fragment of the variable region of the heavy chain with the sequence of SEQ ID NO: 1. 20. Гуманизированное антитело, которое связывается с CD40 человека, содержащее вариабельный участок тяжелой цепи с последовательностью SEQ ID NO:10.20. Humanitariannet antibody that binds to human CD40 containing a variable region of the heavy chain with the sequence of SEQ ID NO: 10. 21. Фармацевтическая композиция для лечения заболеваний, опосредованных Т-клетками, содержащая химерное антитело по п.4 и фармацевтически приемлемый носитель.21. A pharmaceutical composition for treating T-cell mediated diseases, comprising the chimeric antibody of claim 4 and a pharmaceutically acceptable carrier. 22. Фармацевтическая композиция для лечения заболеваний, опосредованных Т-клетками, содержащая химерное антитело по п.6 и фармацевтически приемлемый носитель.22. A pharmaceutical composition for treating T-cell mediated diseases, comprising the chimeric antibody of claim 6 and a pharmaceutically acceptable carrier. 23. Химерное антитело, которое связывается с CD40 человека, содержащее вариабельный участок легкой цепи и вариабельный участок тяжелой цепи, причем указанный вариабельный участок легкой цепи имеет аминокислотную последовательность, по крайней мере, на 90% идентичную последовательности вариабельного участка легкой цепи с последовательностью SEQ ID NO:1.23. A chimeric antibody that binds to human CD40 comprising a light chain variable region and a heavy chain variable region, said light chain variable region having an amino acid sequence that is at least 90% identical to the sequence of the light chain variable region with the sequence of SEQ ID NO :one. 24. Химерное антитело, которое связывается с СD40 человека, содержащее вариабельный участок легкой цепи и вариабельный участок тяжелой цепи, причем указанный вариабельный участок тяжелой цепи имеет аминокислотную последовательность, по крайней мере, на 90% идентичную последовательности вариабельного участка тяжелой цепи с последовательностью SEQ ID NO:2.24. A chimeric antibody that binds to human CD40 comprising a light chain variable region and a heavy chain variable region, said variable heavy chain region having an amino acid sequence that is at least 90% identical to the sequence of the variable region heavy chain sequence SEQ ID NO : 2. 25. Способ лечения больного, страдающего от заболевания, опосредованного Т-клетками, предусматривающий введение указанному больному терапевтически эффективной дозы фармацевтической композиции по п.22.25. A method of treating a patient suffering from a disease mediated by T cells, comprising administering to said patient a therapeutically effective dose of a pharmaceutical composition according to claim 22. 26. Фармацевтическая композиция для лечения заболеваний, опосредованных Т-клетками, содержащая гуманизированное антитело по п.15 и фармацевтически приемлемый носитель.26. A pharmaceutical composition for treating T-cell mediated diseases, comprising the humanized antibody of claim 15 and a pharmaceutically acceptable carrier. 27. Фармацевтическая композиция для лечения заболеваний, опосредованных Т-клетками, содержащая гуманизированное антитело по п.17 и фармацевтически приемлемый носитель.27. A pharmaceutical composition for treating T-cell mediated diseases, comprising the humanized antibody of claim 17 and a pharmaceutically acceptable carrier.
RU2000124084/13A 1998-02-19 1999-02-10 Chimeric antibody that binds with human cd40 (variants), nucleic acid molecule (variants), expression vector (variants), humanized antibody (variants), pharmaceutical composition for treatment of disease mediated by t-cells (variants), method for treatment of patient with diseases mediated by t-cells (variants) RU2220980C2 (en)

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US09/026,291 US6051228A (en) 1998-02-19 1998-02-19 Antibodies against human CD40
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